Conjugated Hyperbilirubinemia Clinical Presentation

Clinical evaluation of those with suspected conjugated hyperbilirubinemia always starts with obtaining a full history.

• Potential toxins (eg, drugs), environmental chemicals (eg, solvents), or wild mushrooms must be carefully excluded. Failure to promptly diagnose toxic hepatitis may result in hepatic failure and death.
• Risk factors for viral hepatitis should be elicited. Possible risk factors include the following:

  • Transfusion
  • Intravenous (IV) drug use
  • Multiple sexual partners
  • Exposure to a person who is infected
• Colicky abdominal pain or fever suggests gallstone disease.
• Weight loss or constitutional systems suggests malignancy or chronic infection.
• Recent anesthesia with the use of halothane suggests halothane hepatitis.
• A history of intense pruritus suggests cholestatic disease resulting from biliary obstruction or intrahepatic cholestasis.
• A family history of jaundice suggests inborn errors of bilirubin metabolism.
• In patients with severe intercurrent illnesses, consider sepsis, hepatic ischemia, and opportunistic infections.
• Severe right heart failure or tricuspid insufficiency with hepatomegaly suggests hepatic congestion.
• Patients on parenteral nutrition may experience cholestasis that sometimes improves with the addition of lipid infusions.
• Patients with acquired immunodeficiency syndrome (AIDS) may experience biliary obstruction from opportunistic infection (eg, AIDS cholangiopathy).
• Patients with chronic liver disease may experience transient elevation of their bilirubin levels following blood transfusion, which results due to a more rapid turnover of the infused cells.
• In patients younger than 20-25 years, a history of a recent flulike syndrome treated with aspirin raises the possibility of Reye syndrome.
• Pregnancy suggests benign recurrent cholestasis or, in late pregnancy, acute fatty liver of pregnancy.
• A categoric listing of the most common diseases that produce conjugated hyperbilirubinemia is presented in the table below. Table. Differential Diagnosis of Conjugated Hyperbilirubinemia

  (Open Table in a new window)

  I. Acute or Chronic Hepatocellular Dysfunction	II. Diseases That Prevent Flow of Bile into the Intestine
  A. Infection	A. Damage to Intrahepatic Bile Ducts or Portal Tracts
  Viral hepatitis A-ECytomegalovirus (CMV) hepatitisEpstein-Barr virus hepatitisSepsis	Primary biliary cirrhosis Graft versus host disease Veno-occlusive disease Sclerosing cholangitis
  B. Inflammation Without Infection	B. Damage to or Obstruction of Larger Bile Ducts
  Toxic liver injuryDrug toxicity (eg, acetaminophen)Halothane hepatitisAlcoholic hepatitisIron overload (hemochromatosis)Copper overload (Wilson disease)Autoimmune hepatitis	Choledocholithiasis Sclerosing cholangitisAIDS cholangiopathyHepatic arterial chemotherapyPostsurgical stricturesBile duct cancersDevelopmental disorders of the bile ducts (eg, Caroli)Extrinsic compression of the bile ductTumorsAcute pancreatitis
  C. Metabolic Dysfunction	C. Diffuse Infiltrative Diseases
  Ischemia ("shock liver")Acute fatty liver of pregnancyAlpha-1 antitrypsin deficiencyPreeclampsiaReye syndromeTotal parenteral nutrition	Granulomatous diseasesSarcoidosisDisseminated mycobacterial infectionsLymphomaWegener granulomatosis Amyloidosis Diffuse malignancy
  D. Inborn Errors of Metabolism	D. Diseases That Interfere with Biliary Secretion of Bilirubin
  Dubin-Johnson syndrome Rotor syndromeBenign recurrent cholestasis	Drug-induced cholestasis, as with the following:- Chlorpromazine- Erythromycin- Estrogens- Anabolic steroids- Many others

• The first manifestation in cases of conjugated hyperbilirubinemia is commonly a brownish discoloration of the urine. Although scleral icterus may also be present, this typically reflects the unconjugated fraction of bilirubin that binds tissues much more avidly.
• If sufficient unconjugated bilirubin is present, the skin, sclerae, and mucous membranes take on a yellow cast, although this may be difficult to detect if the tissues are pigmented naturally.
• Depending on the underlying illness, stigmata of chronic liver disease may or may not be present.
• Palpation of the abdomen may reveal the following:

  • A mass (eg, a distended gallbladder, abdominal tumors)
  • Tenderness over the liver (eg, as in cases of hepatitis or hepatic distention resulting from congestion or infiltrative disease)
  • Tenderness over the gallbladder fossa (as occurs in cases of biliary disease or infection)
• In cases of biliary obstruction or stasis, stool may be acholic and light gray.
• Unexplained darkening of the skin, diabetes, or heart failure suggests hemochromatosis.
• Kaiser-Fleisher rings or a low serum ceruloplasmin concentration suggests Wilson disease.
• Cutaneous or neurologic findings of chronic alcoholism may be helpful diagnostic findings.